20-32208031-C-G

Position:

chr20-32208031-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015352.2(POFUT1):c.90C>G(p.Asp30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000985 in 1,573,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

POFUT1
NM_015352.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0470

Variant links:

Genes affected

POFUT1 (HGNC:14988): (protein O-fucosyltransferase 1) This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

POFUT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20512202).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
POFUT1	NM_015352.2 linkuse as main transcript	c.90C>G	p.Asp30Glu	missense_variant	1/7	ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2 linkuse as main transcript	c.90C>G	p.Asp30Glu	missense_variant	1/5		NP_758436.1
POFUT1	XM_047440079.1 linkuse as main transcript	c.-113C>G		5_prime_UTR_variant	1/6		XP_047296035.1
POFUT1	XR_007067447.1 linkuse as main transcript	n.152C>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8 linkuse as main transcript	c.90C>G	p.Asp30Glu	missense_variant	1/7	1	NM_015352.2	ENSP00000364902	P1	Q9H488-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000787

AC:

AN:

177958

Hom.:

AF XY:

0.0000716

AC XY:

AN XY:

97816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000169

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000214

GnomAD4 exome

AF:

0.000104

AC:

148

AN:

1420928

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

704498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000932

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000425

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dowling-Degos disease 2

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 30 of the POFUT1 protein (p.Asp30Glu). This variant is present in population databases (rs368413950, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with POFUT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 570946). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

D;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.97

D;P

Vest4

0.57

MutPred

0.65

Gain of disorder (P = 0.164);Gain of disorder (P = 0.164);

MVP

0.30

MPC

0.37

ClinPred

0.66

GERP RS

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.83

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over